Development of the S-303 Pathogen Inactivation Technology for Red Blood Cell Concentrates

Abstract

Pathogen inactivation systems are in use in many European countries as routine procedures. However, a pathogen inactivation system for erythrocytes is currently not available. Although significant improvements have been made to decrease the incidence of transfusion-transmitted infections, risks remain for infectious disease agents specific to red blood cell concentrates, such as parasitic infections resulting in babesiosis and malaria. The pathogen inactivation system for erythrocytes utilizes S-303 and glutathione for the treatment of red blood cell concentrates. Preclinical studies to assess the pathogen inactivation efficacy and toxicology as well as preliminary clinical studies have been completed. Preclinical studies have shown log reduction for leukocytes, several viruses and bacteria in excess of 4 to 6 logs. Preclinical toxicology studies were conducted to enable the initiation of two phase III clinical studies in the USA for support of acute and chronic anemia. A second-generation system was developed after observation of an unexpected immune response in two chronic anemia patients. Preclinical pathogen inactivation studies, serological evaluations and a clinical study to evaluate survival of S-303-treated erythrocytes have been completed to support advanced development of the S-303 pathogen inactivation system. A functional system for the inactivation of red blood cell concentrates has been completed and is reaching clinical application.

Phenothiazinium photoantimicrobials with basic side chains

“…proflavine, aminacrine) [5]. In addition, the combination of a planar chromophore and an aminoalkylamino side chain has been used more recently to target nucleic acid, both in anticancer and antiviral applications [6].…”

Pathogen Reduction Technologies: The Best Solution for Safer Blood?

“…A 2 nd generation pathogen inactivation process was developed minimizing the amount of RBC-bound acridine. Preliminary results using this container (n=27) [38] indicated that the treated RBCs maintained sufficient viability (24 hour recovery rates of about 88%) and did not induce positive crossmatches [62].…”

“…The photochemical-based PRT system for erythrocytes has the capacity to effectively reduce pathogens by 4-6 log10 steps but is currently not yet available in routine use [38]. S-303 is composed of an effector (an acridine moiety), a linker (alkyl chain) and an anchor (mustard hydrochloride moiety).…”

Emerging Pathogens - How Safe is Blood?

“…Therefore, the development of new pathogen reduction agents is still needed. The Intercept s303 reagent might be a good candidate, but further field trial studies are needed to analyse its inactivation potential [34]. In addition, riboflavin has also been investigated in clinical trials for packed red cell concentrates and whole blood donations [35].…”